One of the long-term objectives of the Committee on Problems of Drug Dependence (CPDD), and of this program project grant, is to examine the dependence liability of psychotropic substances and to develop improved methodologies to accomplish this. A second, but equally important, objective is to use the results of this research to elucidate the possible mechanisms of action of the substances involved and to provide tools for other investigators studying the process of dependence. The findings from these studies will be utilized by a variety of regulatory agencies (F.D.A., D.E.A., U.N., W.H.O., etc.) in control decisions and by basic research scientists and other groups (e.g., NIDA) interested in the pharmacology and dependence liability of psychotropic substances. The experimental procedures to be used include: an assessment of their general pharmacological profile, physical dependence studies, behavioral toxicity, drug discrimination, and an evaluation of the reinforcing properties of the substances. A variety of animal species will be used including rodents, rhesus monkeys and baboons. All studies will be carried out in a blind fashion to eliminate experimental bias. The Drug Evaluation Subcommittee of the CPDD will monitor and coordinate the activities of this multifaceted drug evaluation and testing program. A consortium of laboratories have been put together to carry out this program project. These include: Washington University School of Medicine (Overall Management and Coordination for the CPDD), National Institute of Diabetes and Digestive and Kidney Diseases (substance coding, analysis and distribution), Virginia Commonwealth University (pharmacological profile and physical dependence assessments), University of Chicago (drug discrimination), University of Michigan (reinforcing properties) and Johns Hopkins University (drug discrimination, reinforcing properties, physiological dependence, and behavioral toxicity). The substances to be tested will come from a variety of sources, such as governmental agencies (e.g., NIDA and DEA), W.H.O., academic institutions and pharmaceutical companies. They will be coded, analyzed chemically, and distributed to the various laboratories as needed for evaluation. The primary screens will be carried out in rodents to obtain relative dose ranges prior to studies in primates. Drug discrimination and self-administration studies will then follow. A more detailed study of reinforcing efficacy and behavioral toxicity will be carried out on selected substances where warranted.